Outline

Background

A C825T polymorphism has been described in the gene GNB3 encoding the G-protein b3 subunit, the T-allele being associated with hypertension and obesity. The underlying pathophysiological mechanisms have not been defined conclusively. Insulin has vasodilatory effects contributing to basal vascular tone. We performed this study to investigate the relevance of the GNB3 C825T polymorphism for the vascular response to insulin.

Methods

We used the linear variable transducer technique to compare dorsal hand vein compliance in 31 young, healthy males with (n = 16 CT/TT) and without (n = 15 CC) the T-allele. After individual dose response curves to phenylephrine (3.2 - 10000 ng/min) had been established, veins were preconstricted to 70 % of their maximum constriction. Then insulin was infused (0,000025 - 0,25 IU/min.) and the venous vasodilatory response was measured. Serum insulin and plasma glucose concentrations were monitored regularly. Plasma glucose was maintained in the range of 80 - 100 mg/dl by infusion of a 10% glucose solution.

Results

The vasodilatory response to insulin was significantly reduced in T-allele carriers as compared to the CC subjects (ANOVA, p= 0.0009). Phenylephrine induced dose-dependent vasoconstriction with no significant difference between genotypes. There were no differences in plasma glucose or serum insulin concentrations between groups.

Conclusion

Our study showed a reduced vasodilatory response to insulin in young, healthy, non-obese C825T-allele carriers. This is in line with results in hypertensive patients and implicates the early presence of a decreased insulin mediated vasodilation as a pathogenetic factor in hypertension development.